| Characteristic | Overall N = 1801 |
ABC N = 301 |
ACB N = 301 |
BAC N = 301 |
BCA N = 301 |
CAB N = 301 |
CBA N = 301 |
p-value2 |
|---|---|---|---|---|---|---|---|---|
| Age (years) | 32 (8) [18, 45] | 33 (8) [19, 44] | 31 (7) [18, 42] | 31 (7) [20, 44] | 33 (8) [19, 45] | 32 (7) [21, 44] | 31 (7) [20, 44] | 0.6 |
| Race | 0.9 | |||||||
| Black | 64 (36%) | 12 (40%) | 13 (43%) | 12 (40%) | 10 (33%) | 8 (27%) | 9 (30%) | |
| White | 52 (29%) | 8 (27%) | 9 (30%) | 7 (23%) | 7 (23%) | 12 (40%) | 9 (30%) | |
| Other | 64 (36%) | 10 (33%) | 8 (27%) | 11 (37%) | 13 (43%) | 10 (33%) | 12 (40%) | |
| Female | 81 (45%) | 13 (43%) | 11 (37%) | 16 (53%) | 14 (47%) | 12 (40%) | 15 (50%) | 0.8 |
| 1 Mean (SD) [Min, Max]; n (%) | ||||||||
| 2 Kruskal-Wallis rank sum test; Pearson’s Chi-squared test | ||||||||
No apparent difference in starting value by period or treatment, so looking at change from baseline in PK
Notation: \(k =\) subject, \(i =\) sequence, \(j =\) period,
\[ \begin{align} k:& \text{subject}, k = 1,...,180\\ j:& \text{sequence}, j=0,1,2\\ i:& \text{period}, i=1,2,3\\ \pi:& \text{period effect}\\ \tau:& \text{treatment effect}\\ \lambda:& \text{sequence/carryover effect}\\ b:& \text{subject-specific intercepts}\\ \varepsilon:& \text{residual error}\\ \end{align} \]
{ijk}:& \ {ijk}:& \
\[ Y_{ik} = \mu + b_{ik} + \pi_i + \tau_{i} + \lambda_i+\varepsilon_{ik}, \quad b_{ik} \sim N(0, \sigma_b^2), \quad \varepsilon_{ik} \sim N(0, \sigma^2) \]
Findings: Significantly less decrease in gels vs pill A
| Comparison | Beta | 95% CI | p-value |
|---|---|---|---|
| Intercept (Pill A, Period 1, Sequence 0) | 120.7 | 115.5, 125.9 | <0.001 |
| Treatment | <0.001 | ||
| Gel B vs Pill A | -10.9 | -15.5, -6.3 | |
| Gel C vs Pill A | -11.7 | -16.2, -7.1 | |
| Period | 0.7 | ||
| Period 2 vs Period 1 | -1.5 | -6.1, 3.1 | |
| Period 3 vs Period 1 | -1.7 | -6.3, 2.9 | |
| Sequence | 0.6 | ||
| Sequence 1 vs Sequence 0 | 2.3 | -2.9, 7.4 | |
| Sequence 2 vs Sequence 0 | 2.4 | -2.7, 7.6 | |
| Abbreviation: CI = Confidence Interval | |||
\[ Y_{i} = \mu + \pi_i + \tau_{i} + \lambda_{i} + \varepsilon_{i}, \quad \varepsilon_{i} \sim N(0, \sigma^2) \]
Findings: Significantly less decrease in gels vs pill A
| Comparison | Beta | 95% CI | p-value |
|---|---|---|---|
| Intercept (Pill A, Period 1, Sequence 0) | 205.9 | 197.7, 214.1 | <0.001 |
| Treatment | <0.001 | ||
| Gel B vs Pill A | -32.4 | -40.0, -24.8 | |
| Gel C vs Pill A | -41.9 | -49.5, -34.3 | |
| Period | 0.8 | ||
| Period 2 vs Period 1 | 2.5 | -5.1, 10.1 | |
| Period 3 vs Period 1 | 1.3 | -6.3, 8.9 | |
| Sequence | 0.7 | ||
| Sequence 1 vs Sequence 0 | -2.9 | -10.5, 4.6 | |
| Sequence 2 vs Sequence 0 | -1.9 | -9.5, 5.7 | |
| Abbreviation: CI = Confidence Interval | |||
\[ Y_{i} = \mu + \pi_i + \tau_{i} + \lambda_{i} + \alpha_{i} + \beta_{i} +\varepsilon_{i}, \quad \varepsilon_{i} \sim N(0, \sigma^2) \]
Skin/Blood PK ~ Random Intercept (Subject) + Treatment + Adherence + Carryover + Period
##
## Call:
## lm(formula = skinVL_change ~ treatment + overall_adhere + overall_safety +
## sequence_ind + period, data = merged)
##
## Residuals:
## Min 1Q Median 3Q Max
## -109.465 -21.844 0.291 21.087 115.767
##
## Coefficients:
## Estimate Std. Error t value Pr(>|t|)
## (Intercept) 107.5583 10.0754 10.675 < 0.0000000000000002
## treatmentGel B -24.3354 3.6291 -6.706 0.0000000000514
## treatmentGel C -36.9474 3.5469 -10.417 < 0.0000000000000002
## overall_adhere 1.8330 0.2753 6.658 0.0000000000696
## overall_safetyNo Adverse Event 56.3456 5.2241 10.786 < 0.0000000000000002
## sequence_ind1 -5.7254 3.4564 -1.656 0.0982
## sequence_ind2 -3.0500 3.4499 -0.884 0.3770
## periodperiod2 0.8405 3.4511 0.244 0.8077
## periodperiod3 1.6260 3.4483 0.472 0.6375
##
## (Intercept) ***
## treatmentGel B ***
## treatmentGel C ***
## overall_adhere ***
## overall_safetyNo Adverse Event ***
## sequence_ind1 .
## sequence_ind2
## periodperiod2
## periodperiod3
## ---
## Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##
## Residual standard error: 32.71 on 531 degrees of freedom
## Multiple R-squared: 0.3614, Adjusted R-squared: 0.3517
## F-statistic: 37.56 on 8 and 531 DF, p-value: < 0.00000000000000022
| Comparison | Beta | 95% CI | p-value |
|---|---|---|---|
| Intercept (Pill A, Period 1, Sequence 0, No Adherence or AE) | 107.6 | 87.8, 127.4 | <0.001 |
| Treatment | <0.001 | ||
| Gel B vs Pill A | -24.3 | -31.5, -17.2 | |
| Gel C vs Pill A | -36.9 | -43.9, -30.0 | |
| Additional Day of Adherence | 1.8 | 1.3, 2.4 | <0.001 |
| Adverse Event | <0.001 | ||
| Adverse Event | — | — | |
| No Adverse Event | 56.3 | 46.1, 66.6 | |
| Sequence | 0.3 | ||
| 1 vs 0 | -5.7 | -12.5, 1.1 | |
| 2 vs 0 | -3.1 | -9.8, 3.7 | |
| Period | 0.9 | ||
| Period 2 vs Period 1 | 0.8 | -5.9, 7.6 | |
| Period 3 vs Period 1 | 1.6 | -5.1, 8.4 | |
| Abbreviation: CI = Confidence Interval | |||
\[ Y_{ik} = \mu + b_{ik} + \pi_i + \tau_{i} + \lambda_{i} + \alpha_{ik} + \beta_{ik} + \varepsilon_{ik}, \quad b_{ik} \sim N(0, \sigma_b^2), \quad \varepsilon_{ik} \sim N(0, \sigma^2) \]
| Comparison | Beta | 95% CI | p-value |
|---|---|---|---|
| Intercept (Pill A, Period 1, Sequence 0, No Adherence or AE) | 72.7 | 59.3, 86.1 | <0.001 |
| Treatment | <0.001 | ||
| Gel B vs Pill A | -6.8 | -11.4, -2.2 | |
| Gel C vs Pill A | -9.1 | -13.6, -4.6 | |
| Additional Day of Adherence | 0.9 | 0.6, 1.3 | <0.001 |
| Adverse Event | <0.001 | ||
| Adverse Event | — | — | |
| No Adverse Event | 26.4 | 19.6, 33.2 | |
| Sequence | 0.7 | ||
| 1 vs 0 | 0.9 | -3.8, 5.7 | |
| 2 vs 0 | 1.9 | -2.9, 6.6 | |
| Period | 0.6 | ||
| Period 2 vs Period 1 | -2.3 | -6.7, 2.1 | |
| Period 3 vs Period 1 | -1.5 | -5.9, 2.8 | |
| Abbreviation: CI = Confidence Interval | |||